Drug Interaction Report

GENERALLY AVOID: Concomitant use with multiple doses of vorasidenib may decrease the plasma concentrations of drugs that are substrates of CYP450 3A. Vorasidenib is predicted to be an inducer of CYP450 3A resulting in decreased plasma concentrations of agents that are metabolized by the isoenzyme. The interaction may be significant for sensitive CYP450 3A4 substrates or those that demonstrate a narrow therapeutic index. Clinical and pharmacokinetic data are currently lacking.

MANAGEMENT: Concomitant use of vorasidenib with substrates of CYP450 3A should be avoided due to the potential for reduced efficacy

ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.

GENERALLY AVOID: Due to induction of CYP450 1A2, the isoenzyme primarily responsible for the metabolic clearance of vorasidenib, smoking tobacco during treatment with vorasidenib may decrease its plasma concentrations and anti-tumor effect. Clinical and pharmacokinetic data are currently lacking.

MANAGEMENT: Patient should be advised to avoid smoking tobacco during treatment with vorasidenib because it may reduce efficacy of the therapy.